EVALUATION OF PORFIMER SODIUM FLUORESCENCE FOR MEASURING TISSUE TRANSFORMATION

Background. Neoplastic tissue can be detected by its increased fluores cence compared with surrounding normal tissue after the injection of t he tumor-localizing compound porfimer sodium (Photofrin; Quadra Logic Technologies, Vancouver, BC, Canada). In vivo fluorescence photometry is a nonimaging photodetector technique that detects specific 690 nm f luorescence of the porphyrin by subtracting nonspecific 612 nm excitat ion from 630 nm excitation. The technique was applied in the developme ntal stages of the 9,10 dimethyl-1,2-benzanthracene (DMBA)-induced ham ster buccal cheek pouch carcinoma model to (1) quantitate and characte rize porfimer sodium fluorescence and uptake as it relates to lesion p rogression and biochemical changes and (2) determine whether porfimer sodium-induced fluorescence will vary with promotional and inhibitory stimuli. Methods. Groups of Syrian Golden hamsters had their cheek pou ch buccal mucosa exposed to a 0.5% DMBA in acetone three times per wee k for 6 weeks (premalignant lesions), 12 weeks (squamous cell carcinom as), or other specified durations. The rate of malignant transformatio n was either promoted (by either carbon dioxide laser incision or cont inued DMBA application) or inhibited (by the administration of either somatostatin analogue RC-160 [D-Phe-Cys-Tyr-D-Trp-Lys-Val-Cys-Trp-NH2] or bombesin antagonist RC-3095 pi-Gln-Trp-Ala-Val-Gly-His-Leupsi(CH2N H)Leu-NH2]). Groups of DMBA-exposed hamsters were subsequently injecte d with 1.0 mg/kg of porfimer sodium during the various stages of tumor development. Twenty-four hours after injection, fluorescence levels w ere measured by in vivo fluorescence photometry. Samples of tumors, dy splastic mucosal tissue, and normal-appearing oral mucosa were biopsie d and used for either tissue extraction assays, histopathologic examin ation, or tyrosine kinase activity assay as an index of rate of transf ormation. Results. Results demonstrated that porfimer sodium is retain ed in DMBA-treated tissue. Fluorescence is completely accounted for by porfimer sodium uptake. The duration of exposure to carcinogen is pro portional to porfimer sodium fluorescence. This relationship establish es that premalignant lesions can be distinguished from normal tissue b y porfimer sodium uptake and fluorescence. The changes in increased ty rosine kinase activity paralleled the increase in porfimer sodium fluo rescence. Alterations in the rate of tissue transformation produced eq uivalent alterations in porfimer sodium-induced fluorescence. Conclusi ons. These results suggest that porfimer sodium uptake and fluorescenc e can be used in a prognostic manner to diagnose and determine the cou rse of transformation of individual lesions.